Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer’s disease: a cross-ethnic, cross-platform validation study

Relative importance of blood-based biomarkers for Alzheimer’s disease-specific neurodegeneration and cognitive decline

A stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.

Blood-based multimodal biomarker models for differentiating early-onset Alzheimer’s disease from frontotemporal dementia: a longitudinal study of early-onset dementia and family members (LEAF) study

Cross-Sectional and Longitudinal Diagnostic Performance of Plasma p-tau217 and p-tau217/Aβ42 in Alzheimer's Disease.

OBJECTIVE Recent studies suggest that combining plasma phosphorylated tau (p-tau) with β-amyloid (Aβ) may improve diagnosis accuracy for Alzheimer's disease (AD). However, the cross-sectional and longitudinal concordance of these markers with Aβ positron emission tomography (PET) positivity remains incompletely understood. This study aimed to evaluate the diagnostic performance of plasma p-tau, alone and in combination with plasma Aβ, in AD. METHODS We included 326 participants from the Alzheimer's Disease Neuroimaging Initiative and 357 Chinese older adults from the Greater-Bay-Area Healthy Aging Brain Study who underwent Aβ-PET imaging. Longitudinal data were available for 285 Alzheimer's Disease Neuroimaging Initiative participants. Plasma p-tau181, p-tau217, Aβ42, and Aβ40 were measured on different analytical platforms. Diagnostic performance for Aβ-PET positivity was assessed using a two-cutoff approach. RESULTS Combining plasma p-tau with Aβ42 or the Aβ42/40 ratio reduced the intermediate zone. Notably, p-tau217/Aβ42 showed stronger agreement with Aβ-PET positivity than p-tau217 alone. Among individuals classified as p-tau217/Aβ42 positive but p-tau217 intermediate, 57.1 to 83.3% were Aβ-PET positive. Longitudinally, most Stable Positive (88.0-96.1%) and Stable Negative (89.4-90.9%) cases defined by p-tau217 or p-tau217/Aβ42 were Aβ-PET positive and Aβ-PET negative, respectively. Critically, 69.7 to 75.8% of Non-positive to Positive cases defined by p-tau217/Aβ42 were Aβ-PET positive. INTERPRETATION These findings provide novel insights into the cross-sectional and longitudinal diagnostic performance of plasma p-tau217/Aβ42 in AD. To be specific, plasma p-tau217/Aβ42 can reduce the intermediate zone and improve agreement with Aβ-PET positivity, and longitudinal p-tau217/Aβ42 monitoring is particularly informative for identifying Aβ-PET-positive patients who were p-tau217/Aβ42 negative or intermediate at baseline and were misclassified as low risk of AD. ANN NEUROL 2026.

Predictive value of plasma p-tau217 for Alzheimer’s dementia compared to other blood-based biomarkers

Phosphorylated-tau (p-tau217) is a promising blood-based biomarker for Alzheimer’s dementia (AD) in clinical settings. However, research from prospective cohort studies is sparse. We measured plasma p-tau217 levels in baseline blood samples of 779 participants in a population-based cohort of older adults followed over 17 years. Associations with AD were assessed and compared to those with previous measurements of p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Comparisons to the amyloid beta (Aβ) misfolding biomarker were performed in a subgroup analysis. P-tau217, NfL and GFAP showed strong associations with AD risk, especially within the first 9 years of follow-up, outperforming p-tau181. Over the later years of follow-up, the predictive accuracy of p-tau217 was significantly reduced. In contrast, the Aβ misfolding biomarker demonstrated superior performance especially as a preclinical indicator of the risk of AD many years before diagnosis. The combination of p-tau217 with NfL, GFAP, basic demographic and genetic information, as well as the misfolding biomarker yielded an AUC 0.86 for AD diagnoses over the entire 17-year follow-up period. P-tau217 is a promising blood-based biomarker for Alzheimer’s dementia (AD) in the clinical stage. In this prospective cohort study, it showed better performance in the prodromal than in the preclinical stage up to 17 years before diagnosis. In a subgroup analysis, the Aß misfolding biomarker showed higher discriminative ability in the preclinical stage compared to p-tau217. A prediction model including p-tau217, NfL, GFAP, Aß misfolding as well as basic demographic and genetic information reached an AUC of 0.86 for AD over the entire follow-up period. In a subgroup analysis, the Aß misfolding biomarker showed higher discriminative ability in the preclinical stage compared to p-tau217. A prediction model including p-tau217, NfL, GFAP, Aß misfolding as well as basic demographic and genetic information reached an AUC of 0.86 for AD over the entire follow-up period. P-tau217 is a promising blood-based biomarker for Alzheimer’s dementia (AD) in the clinical stage. In this prospective cohort study, it showed better performance in the prodromal than in the preclinical stage up to 17 years before diagnosis.

Serum p-Tau217 and apolipoprotein E as potential biomarkers for Alzheimer's disease severity: a case-control study

Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative illness characterised by aberrant protein accumulation and progressive cognitive decline. One of the most researched blood indicators of tau pathology is phosphorylated tau 217 (p-tau217), and apolipoprotein E (ApoE) is essential for lipid metabolism, amyloid removal, and neuronal maintenance. The severity of AD may be correlated with changes in these biomarkers. Objective: To compare serum levels of p-tau217 and ApoE in individuals with different severities of Alzheimer's Disease. Methods: The present case–control study consisted of 156 subjects aged between 55 and 85 years:106 patients with ad (and balanced frequency matched to healthy controls on age, international classification of diseases t63 diagnosis). The DSM-5 criteria classified the patients as mild (n = 12), moderate (n = 50), or severe (n = 44). Using the sandwich enzyme-linked immunosorbent assay (ELISA), the levels of circulating ApoE and p-tau217 were determined. The receiver operating characteristics (ROC) curve examination, Spearman's correlation, and the Kruskal-Wallis test were used in the statistical studies. Results: The mean serum p-tau217 and ApoE level were 165 ± 84.2 pg/mL and 75.5 ± 55.6 ng/mL, respectively. While serum p-tau217 significantly increased with severity of disease, ApoE levels decreased. We found a significant positive association of p-tau217 (p<0.001) and a negative association of ApoE (p<0.001) with disease severity by DSM-5 criteria. ROC analysis showed high diagnostic accuracy of CSF p-tau217 (AUC=0.916, sensitivity: 87.18%, specificity: 90.00%) and ApoE (AUC=0.992, sensitivity: 100.00%, specificity:98.00%). Conclusion: Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity. Both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.   Objectives: The study objective is to reveal biochemical way to diagnose and know Alzheimer's patients biochemically instead of using traditional Methods that used to diagnosis as an example using: Electroencephalography (EEG), computed tomography (CT), magnetic resonance imaging (MRI) and brain biopsy.   Methods: A case control research design was applied to current study, 156 individuals and thy were as follows: 12 with mild symptoms ,50 with moderate,44 with sever progression and 50 apparently as healthy control with an age range of 55 to 85 years were included. Samples were collected in accordance with the consultant's diagnosis; disease severity was categorized according to DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) staging, which was then demonstrated by laboratory tests. A Human p-tau217 (Phospho Tau 217) Catalogue No.: EH5067 Revision: V4.0 Size: 48T/96T ELISA Kit was used and rang test was (7.813-500pg/ml) which tested by instrument (human reader). Results: The baseline serum biomarkers analysis of whole Study Participants showed that the mean tau level was 165 ± 84.2 pg/mL, Tau levels increased markedly with disease severity, rising from 86.33 ± 34.40 pg/mL in the control group to 265.72 ± 50.91 pg/mL in the severe group. DSM-5 score also showed a strong positive correlation with Tau concentration, suggesting that higher clinical severity was associated with increased Tau levels. Tau showed very strong negative correlations with ApoE, the correlations' findings indicated that this effect size is substantial up to assay. ApoE demonstrated a mean value of 75.5 ± 55.6 ng/mL. of whole Study Participants. ApoE levels showed a pronounced and significant reduction across disease stages, with the lowest mean value observed in the severe group. While DSM-5 score also showed a negative association with ApoE was strong and significant.   Conclusion: Serum Tau levels increased markedly with disease severity, indicating that Tau may serve as a reliable marker of progressive neuronal injury and neurodegeneration in Alzheimer’s disease. ApoE levels declined substantially with increasing disease severity and showed the highest diagnostic accuracy among the studied biomarkers, indicating its strong potential as a predictive biomarker for Alzheimer’s disease progression.

Diagnostic Performance of the AlzoSure Predict Assay and Its Association With Alzheimer's Disease Biomarkers and Imaging Findings

ABSTRACT Background Early diagnosis of Alzheimer's disease (AD) is critical for improving patient outcomes. The laboratory‐developed blood test of AlzoSure measures the unfolded conformational variant of p53 (U‐p53AZ) in plasma and has shown promise as a screening tool for AD risk. We aimed to evaluate the association between U‐p53AZ with established cerebrospinal fluid (CSF) and neuroimaging measures, and to determine its diagnostic performance in distinguishing cognitively normal (CN) individuals from those with mild cognitive impairment (MCI). Methods Participants included CN and MCI individuals aged 55–90 years with complete baseline and 24‐month follow‐up assessments. Associations between U‐p53AZ, CSF biomarkers, standardized uptake value ratio (SUVR) of glucose measured by fluorodeoxyglucose positron emission tomography (FDG‐PET), and cognition were examined with multivariable regression models adjusted for age, sex, and APOE ε4 status. Diagnostic performance was assessed with receiver operating characteristic (ROC) analysis. Results At baseline, no significant group differences were observed in plasma U‐p53AZ, FDG SUVR, or CSF biomarkers between CN and MCI. Longitudinally, FDG SUVR significantly declined in MCI (p = 0.040), while CSF t‐tau and p‐tau181 increased in both groups (all p < 0.05). Higher U‐p53AZ levels were independently associated with elevated CSF t‐tau (β = 0.38; p = 0.033) and p‐tau181 (β = 0.37; p = 0.033) at baseline, and these associations persisted at follow‐up (β range 0.43–0.48; all p < 0.02). No significant associations were found with FDG SUVR or cognitive scores. The discriminative ability of U‐p53AZ to distinguish CN from MCI was modest (AUC = 0.617, 95% CI 0.518–0.716). Conclusion AlzoSure measurements are significantly associated with CSF tau values but demonstrate limited utility in differentiating CN from MCI. Although promising as a marker of tau‐related neurodegeneration, AlzoSure has a modest diagnostic performance as a stand‐alone assessment.